This invention relates generally to the medical field and, more particularly, to the use of photodynamic therapy in organ augmentation, for example, enterocystoplasty or colocystoplasty or the use of other gasto-intestinal segments for organ augmentation. The present invention involves treatment of a patient using a photosensitive composition which selectively accumulates in mucosal tissues.
It is to be understood that the present invention is useful for augmentation of various organs. For ease of illustration, the specification herein describes in detail augmentation of a bladder organ using gastro-intestinal tissue. It is within the contemplated scope of the present invention that other organs using various tissues as augment are within the scope of the claimed invention.
The surgical treatment involved in augmentation of an organ involves exposing a portion of gastro-intestinal tissue (including stomach, large bowel (colon) and small intestine) and transplanting or inserting the exposed intestinal tissue into the organ. It is to be noted that various recipient organs such as the bladder, stomach and other portions of the gastro-intestinal tract, such as esophagus and the like, are contemplated as being within the scope of the present invention. In particular, bladder augmentation has been principally used in the treatment of patients with tuberculosis of the bladder, interstitial cystitis and bladder cancer. Currently, bladder augmentation is gaining wider acceptance as a therapeutic option for patients that have small, non-compliant bladders and for treating the variety of congenital, inflammatory and neoplastic problems in the urinary bladder which are refractory to medical management. Medical indications for bladder augmentation include fibrosed and scarred bladders from previous surgery, radiation therapy, or trauma; small non-compliant bladders associated with extrophy and epispadias; and, neurogenic bladders associated with myelodysplasia.
Despite significant advances in patient treatment using organ augmentation, there is a need for an improved augmentation procedure since numerous complications are associated with incorporating intestinal mucosa into the recipient organ. These complications include metabolic and electrolyte disturbances, such as hyperchloremic metabolic acidosis and hypokalemia; chronic bacterial colonization, which results in infections and/or sepsis; formation of stones or lithiasis; or malignant transformation at the vesicoenteric anastomosis. Still other complications arise from the fact that the intestinal mucosa continues to produce mucus after being transplanted into the recipient organ. The continued mucus production causes problems in patients. In bladder augmentation, for example, the continued mucus production requires frequent catheterization to prevent blockages in the genitourinary tract.
One attempt to overcome these complications involves mechanical stripping of the bowel mucosa layer while leaving the underlying submucosa and muscular layers intact. This mechanical stripping does lead to a decrease in mucus production. However, in the animal models tested, there is often marked retraction and fibrosis of the intestinal segment with little or no gain in organ capacity. The retraction and lack of increased organ capacity defeats the purpose of organ augmentation. Further, this type of mechanical surgical stripping of the mucosa is technically tedious and has limited potential application to humans.
Therefore, it is important that a method for organ augmentation include a way to decrease or prevent mucus production by the transplanted intestinal tissue while maintaining the elastic and muscular integrity of the transplanted tissue. The present invention addresses this problem.
In photodynamic therapy, photosensitive compositions are used to selectively diagnose, alter or destroy pathologic tissue. For example, photosensitive compounds are used which differentially localize in a target tumorous tissue where the compositions absorb electromagnetic radiation when irradiated. The photosensitive compositions are useful due to their ability to differentially localize in the target tissue as compared to the amount absorbed by the surrounding non-cancerous or normal tissues and produce toxic reactions when activated.
For example, photosensitive compositions have been proposed as useful compounds for topical applications for diagnosis and treatment of skin diseases. In addition, photosensitive compositions have been proposed for use to sterilize biological samples containing infectious agents such as bacteria and viruses. The bactericidal effects are induced by irradiation of tissues with photosensitive compositions against gram-negative and gram-positive microorganisms (Martinetto et al., Drugs Exp. Clin. Res. XII (4) 335-342, 1986). The photosensitive compositions have also been used to decontaminate blood and blood components. In addition, photosensitive compositions have been used in the treatment of blood vessel occlusions such as atherosclerotic plaques, thrombi and the like. Photodynamic therapy in combination with hyperthermia has also been proposed as a useful method in treating many of these disorders or diseases. Photosensitive compositions have also been proposed as useful in the diagnosis of disease. These photosensitive compositions have fluorescent properties and since the photosensitive compositions sequester in diseased tissues, fluorescent visualizations and/or measurement can be used to diagnose and localize the disease or to direct therapy to the affected tissues.
Until the present invention, there has been no suggestion of using photodynamic therapy in the in vivo treatment of benign protocol for patients who will benefit from intestinal mucosa transplanted into an organ.